Cartilage within lipomyelomeningocele and ulnar longitudinal deficiency syndrome as VACTERL association, alliance in SHH/GLI3, and Wnt pathway: illustrative case.

BACKGROUND: Lipomyelomeningocele associated with an ulnar club hand in the spectrum of VACTERL association ([costo-]vertebral abnormalities; anal atresia; cardiac defects; tracheal-esophageal abnomalities, including atresia, stenosis, and fistula; renal and radial abnormalities; limb abnormalities; single umbilical artery) is a very rare and infrequently reported phenomenon. Within the fat mass of the lipoma, it is not common to find a well-defined cartilaginous mass with no attachments to the surrounding tissue. OBSERVATIONS: The authors present the case of a 3-month-old male with low-back swelling that was off-center to the left, accompanied by a left short forearm displaying outward bowing. Echocardiography showed an atrial septal defect. This rare VACTERL association comprises lipomyelomeningocele, atrial septal defect, and ulnar longitudinal deficiency syndrome. During surgical intervention for the lipoma, a well-defined cartilaginous mass was discovered within the adipose tissue. LESSONS: The manifestation of VACTERL association can be partially explained by the Shh/Gli and Wnt pathway defects. It is prudent to screen children with neural tube defects to be aware of any associated syndromes. This case is very rare, and the literature has contained no prior report on the VACTERL association of lipomyelomeningocele, atrial septal defect, and ulnar longitudinal deficiency.

Computer Vision Syndrome and Associated Factors Among Secretaries Working in Ministry Offices in Addis Ababa, Ethiopia.

BACKGROUND: Prolonged use of computers led users to risk of computer vision syndrome (CVS). CVS is one of the occupational health problems. The aim of this study was to assess CVS and associated factors among secretaries working in government ministry offices in Addis Ababa, Ethiopia. MATERIALS AND METHODS: Institution-based cross-sectional study was conducted. Data were collected using interviewer administered pretested structured questionnaire and ophthalmic examinations. A total of 455 secretaries were participated in the study. Binary logistic regression analysis was applied to investigate determinants associated with CVS. Variables with p-value <0.05 were considered statistically significant. RESULTS: The prevalence of CVS among secretaries working in ministry offices in Addis Ababa was 68.8%. The main reported symptoms were blurred vision (36.9%), eye strain (32.1%), redness of the eye (27.3%) and headache (26.4%). Average monthly income (AOR=0.453, 95% CI: 0.235-0.874), habit of frequent voluntary blinking (AOR=0.313, 95% CI: 0.150-0.655), taking regular breaks between work (AOR=0.279, 95% CI: 0.078-0.996), using computer eye/glasses/spectacles (AOR=0.451, 95% CI: 0.245-0.830), sources of light at work place (AOR=0.009, 95% CI: 0.001-0.076), using an antiglare filter (AOR=0.216, 95% CI: 0.117-0.401) and knowledge (AOR=0.212,95% CI:0.115-0.389) were significantly associated with CVS. CONCLUSION: Prevalence of CVS among secretaries was high. Average monthly income, habit of voluntary blinking, taking regular break, using computer spectacles, sources of light at work place, using an antiglare filter and knowledge were significantly associated with CVS. The findings suggest the need for adjusting exposure time to computers and increase awareness on safety measures and regular eye screening.

Profiling of Inflammatory Proteins in Plasma of HIV-1-Infected Children Receiving Antiretroviral Therapy.

Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-α, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.

Streptococcus pneumoniae Nasopharyngeal Carriage among PCV-10-Vaccinated HIV-1-Infected Children with Maintained Serological Memory in Ethiopia.

Streptococcus pneumoniae (S. pneumoniae) vaccines have substantially reduced the burden of invasive pneumococcal diseases (IPDs) worldwide. Despite high coverage with S. pneumoniae vaccination, upper-respiratory-tract colonization by S. pneumoniae is still common. We assessed maintenance of serological responses to S. pneumoniae serotypes included in PCV-10 by ELISA in HIV-1-infected children (n = 50) and age-matched controls (n = 50) in Ethiopia. We isolated S. pneumoniae in nasopharyngeal swabs and determined S. pneumoniae serotype by whole genome sequencing (WGS). Comparable levels of S. pneumoniae serotype-specific IgG concentrations were detected in plasma of HIV-1-infected children and matched controls, with geometric mean concentrations (GMCs) consistently higher than the protective threshold for PCV-10 serotypes of 0.35 µg/mL. We isolated S. pneumoniae from 38 (out of 97) nasopharyngeal swabs, 25 from HIV-1-infected children and 13 from controls. WGS based serotyping revealed 22 known S. pneumoniae serotypes and 2 nontypeable (NT) isolates. Non-PCV-10 serotypes represented >90% of isolates. We showed that HIV-1-infected children and matched controls in Ethiopia carry a level of maintained serological memory to PCV-10 considered protective for IPDs. We identified a higher proportion of nasopharyngeal carriage with highly pathogenic S. pneumoniae non-PCV strains among HIV-1-infected children compared to controls.

E-Cigarette Exposure Delays Implantation and Causes Reduced Weight Gain in Female Offspring Exposed In Utero.

Electronic nicotine delivery system (e-cigarette) use is prevalent among pregnant women as a seemingly safe alternative to traditional tobacco use, known to result in fetal developmental abnormalities and impaired fertility of male offspring. However, little is known about the effects of e-cigarette use on fertility or pregnancy outcomes. A successful pregnancy is initiated by a multitude of dynamic molecular alterations in the uterus resulting in embryo implantation at day 4.5 in the mouse. We examined whether e-cigarette exposure impairs implantation and offspring health. Pregnant C57BL/6J mice were exposed five times a week to e-cigarette vapor or sham. After 4 months, e-cigarette exposed dams exhibited a significant delay in the onset of the first litter. Furthermore, exposure of new dams in early pregnancy significantly impaired embryo implantation, as evidenced by nearly complete absence of implantation sites in e-cigarette-exposed animals at day 5.5, despite exhibiting high levels of progesterone, an indicator of pregnancy. RNA microarray from day 4.5 pseudopregnant mice revealed significant changes in the integrin, chemokine, and JAK signaling pathways. Moreover, female offspring exposed to e-cigarettes in utero exhibited a significant weight reduction at 8.5 months, whereas males exhibited a slight but nonsignificant deficiency in fertility. Thus, e-cigarette exposure in mice impairs pregnancy initiation and fetal health, suggesting that e-cigarette use by reproductive-aged women or during pregnancy should be considered with caution.

Homing defects of B cells in HIV-1 infected children impair vaccination responses.

BACKGROUND: Successful vaccinations rely on antibody responses. Chemokine receptors play an important role in B cell homing to differentiation niches. We assessed CXCR4, CXCR5 and CCR6 expression on B cells during HIV-1 infection and relate it to antibody responses against a HBV vaccine. METHODS: Blood was obtained from 54 healthy controls and 38 ART-treated HIV-1 infected children, aviremic (n = 25) or viremic (n = 13). Frequency of naïve and memory B cell subsets was studied by immunostaining. Homing capacity of blood B cells to lymphoid and inflamed tissues was evaluated through CXCR4, CXCR5 and CCR6 expression. Plasma CXCL12 and CXCL13 levels and antibody titers to HBV antigen were determined by ELISA. RESULTS: The frequency of naïve and resting memory (RM) B cells in ART treated children was comparable to control subjects. Profound defects in the homing phenotypes of naïve and memory B cells were identified, with lower CXCR4 and CXCR5 expression. Increased CXCL13 levels were observed in infected children, inversely correlating to CXCR5 expressing B cell subpopulations. Antibody titers to HBV vaccine correlated with frequency of resting and switched memory B cells in HIV-1 infected children. CONCLUSIONS: Homing defects of B cells to germinal center may underlie impaired vaccine responses during HIV-1 infection.

T follicular helper cells and antibody response to Hepatitis B virus vaccine in HIV-1 infected children receiving ART.

HBV vaccine has 95% efficacy in children to prevent HBV infection and related cancer. We conducted a prospective study in HIV-1 infected children receiving ART (n = 49) and controls (n = 63) to assess humoral and cellular responses to HBV vaccine provided with three doses under an accelerated schedule of 4 weeks apart. At 1 month post-vaccination all children, except 4 HIV-1 infected, displayed protective antibody (ab) titers to HBV vaccine; ab titers were lower in infected children (P < 0.0001). Ab titers decreased (P < 0.0001) in both HIV-1 infected and control children at 6 months. The frequency of circulating Tfh (cTFh) cells was 20.3% for controls and 20.8% for infected children prior to vaccination and remained comparable post-vaccination. Cytokine expression by cTfh cells upon activation with HBV antigen was comparable in the two groups at baseline and 1 month post-vaccination. Higher plasma levels (P < 0.0001) of CXCL13 were found in infected children which correlated with cTfh cell frequency at baseline. In conclusion, a lower ab response to HBV vaccine was measured in HIV-1 infected children. The frequency and activation profile of cTfh cells was comparable in infected children and controls suggesting that cells other than Tfh cells are responsible for impaired ab response to HBV vaccine.